Insulin enhance phosphorylation of both alpha and beta subunits of its own receptor by stimulation of tyrosine-specific protein kinase which is tightly associated with the receptor itself. The biochemical characterization of this enzyme is being studied under several conditions in order to determine its potential physiological significance. Although the enzyme is tightly associated with the receptor, the phosphorylating mechinery can be distinguished from the insulin binding site itself. Studies in tissue (liver and brain) from rats under two conditions of corticosteroid excess and fasting in which there is a defect in insulin action distal to insulin binding have been carried out. Post-binding defect in insulin action can not be explained by impairment of intrinsic activity of insulin receptor-associated protein kinase.